In this proposal, we will quantitate the effects of autonomic drugs and certain known mediators of immediate hypersensitivity as well as specific antigen in several different segments isolated from the pulmonary vasculature of different species. The segments inlude large and small arteries and veins and our experiments will be directed toward determining differences in sensitivity of the in vitro vascular segments in response to the several chemical substances. The vascular segments will be taken from animals housed in chambers to control for temperature, humidity, altitude and oxygen. Temperature and humidity will remain constant for all groups, but simulated altitude and oxygen concentration will vary to include differet levels and time periods of exposure to hyper-, hypobaria and hyperhypoxia. Experiments to elucidate the mechanism for differing sensitivities and changes in sensitivities due to different environmental conditions are included with a focus on analyses of pharmacological receptor systems. These systems are located at the levels of the smooth muscle, adrenergic neurons, mast cells and endothelial cells. We plan to study contraction and relaxation in response to substances acting at postsynaptic receptors, responses to transmural stimulation and the action of substances on norepinephrine release and responses to immunological challenge and the action of substances on antigen-induced vascular effects. Also, using treatments to modify the numbers of endothelial cells, we will determine if selective histological alterations change pharmacological responses to the several drugs. Results from these studies should lead to a more comprehensive understanding of pharmacological receptor systems (especially autonomic) in pulmonary vasculature and lead to selective therapies.